No evidence of nitrate tolerance caused by nebivolol.

Author(s):Stoschitzky K, Stoschitzky G, Pieske B, Wascher T

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Abstract BACKGROUND: Continuous long-term treatment with nitrates may cause nitrate tolerance. Nebivolol is a highly selective beta1-adrenergic antagonist with additional nitric oxide (NO)-mediated vasodilatory effects. However, there have been no investigations into whether or not the long-term administration of nebivolol might cause nitrate tolerance. METHODS: We performed a randomized, double-blind, placebo-controlled, cross-over study in 16 healthy men. Subjects received 5 mg nebivolol or placebo once daily for 8 days in random order divided by a drug-free interval of 2 weeks. Forearm blood flow (FBF) was measured by venous occlusion plethysmography 3 h after oral intake of the first and last doses of nebivolol and placebo, respectively. FBF was measured again following the intravenous administration of 4 μg nitroglycerin/kg body weight/min for 5 min. RESULTS: Following 8 days of continuous intake of placebo, nitroglycerin increased FBF by 54\% (p < 0.05), whereas nitroglycerin increased FBF by 96\% (p < 0.01) following 8 days of continuous intake of nebivolol, and the increase after 8 days of nebivolol was significantly (p < 0.05) more pronounced than after 8 days of placebo. CONCLUSIONS: These findings indicate no evidence of nitrate tolerance caused by long-term administration of nebivolol. On the contrary, long-term intake of nebivolol increases rather than decreases the NO-mediated vasodilating effects.